Impact of Iron Overload in Higher Risk Myelodysplastic Syndromes

Several studies demonstrated detrimental effect of iron overload and elevated serum ferritin mainly in lower risk myelodysplastic syndromes (MDS). Sanz and his colleagues reported inferior overall survival (OS) and leukemia free survival in patients with elevated serum ferritin ≥ 1000 ng/ml independent from RBC transfusion dependency (TD). Only 22% of the patients in that study were intermediate 2 (int-2) or high risk by international prognostic scoring system (IPSS). Recent studies also suggested inferior outcome with allogeneic stem cell transplant in patients with elevated serum ferritin. We examined the prognostic value of elevated serum ferritin in int-2 and high risk IPSS MDS patients.

We identified int-2 or high risk IPSS MDS patients through Moffitt Cancer Center (MCC) MDS database. Patients were included if serum ferritin levels were available. Patients were divided into 2 groups based on serum ferritin <1000 or ≥ 1000 ng/ml. Individual charts were reviewed. Chi square test and t-test were used to compare baseline characteristics. Kaplan Meier estimates were used to calculate OS from time of referral to MCC, log rank test was used for comparison between the 2 groups and Cox regression analysis was used for multivariable analysis. All analysis was conducted using SPSS version 19.0 software.

We identified 201 MDS patients with int-2 or high risk IPSS evaluated at MCC. Serum ferritin data were available in 139 patients. Serum ferritin ≥ 1000 ng/ml was elevated in 38.3% (n=54). Baseline characteristics compared between the 2 groups included age, WHO subtype, MD Anderson risk model, karyotype, RBC TD, and treatment with azacitidine. No statistical significant differences were observed between the 2 groups except for a trend of more RBC TD in patients with elevated serum ferritin. (Table-1) The median duration of follow up was 34.9 months (95%CI 20.8–49.1). The median OS for patients with serum ferritin < 1000 ng/ml was 15.2 months (95%CI 12.6–17.9) compared to 8.1 months (95%CI 5.7–10.4) in patients with serum ferritin ≥ 1000 ng/ml (P=0.004).(Figure-1) In univariate analysis Age ≥ 60 years, MD Anderson risk group, RBC TD, serum ferritin and serum albumin were statistically significant prognostic factors for OS. In multivariable analysis, Age ≥ 60 years [HR 2.0 (95% CI 1.12–3.7), p=0.02], MD Anderson risk group [HR 1.8 (95%CI 1.3–2.54), p= <0.005], and serum ferritin ≥ 1000 ng/ml [HR 1.6 (95%CI 1.1–2.5), p=0.02] were independent prognostic factors for OS.The rate of AML transformation was 25.9% compared to 44.4% in patients with serum ferritin < 1000 and ≥ 1000 ng/ml respectively, p=0.039. This effect was not significant after adjusting for RBC TD.

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Kaplan Meier estimates of overall survival based on serum ferritin levels

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Kaplan Meier estimates of overall survival based on serum ferritin levels

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Elevated serum ferritin level ≥ 1000 ng/ml in int-2 and high risk IPSS MDS was independently associated with worse OS and higher rate of AML progression. Those findings needs to be confirmed in larger cohort of patients and prospectively.

No relevant conflicts of interest to declare.